|
rs121913377
|
|
melanoma
|
|
0.800 |
GeneticVariation
|
BEFREE |
Correlative preclinical studies demonstrated broad activity for E6201 across BRAF V600E mutant melanoma cell lines and effective BBB penetration in vivo.
|
30264293 |
2019 |
|
rs121913377
|
|
melanoma
|
|
0.800 |
GeneticVariation
|
BEFREE |
Overall these data highlight the potential of ganetespib as a single-agent or combination treatment in BRAF(V600E)-driven melanoma, particularly as a strategy to overcome acquired resistance to selective BRAF inhibitors.
|
24398428 |
2014 |
|
rs121913377
|
|
melanoma
|
|
0.800 |
GeneticVariation
|
BEFREE |
Among 23 melanomas located at body sites with chronic UV exposure, only a single tumour harboured the B-raf V599E mutation (4%), which was a significantly lower frequency in comparison to melanomas from sun-protected body sites (26%; Fisher's exact test, p=0.038; odds ratio, 7.59).
|
16773193 |
2006 |
|
rs121913377
|
|
melanoma
|
|
0.800 |
GeneticVariation
|
BEFREE |
Thus, when present, BRAF(V599E) appears to be essential for melanoma cell viability and transformation and, therefore, represents an attractive therapeutic target in the majority of melanomas that harbor the mutation.
|
14500344 |
2003 |
|
rs121913377
|
|
melanoma
|
|
0.800 |
GeneticVariation
|
BEFREE |
Patients with BRAF V600E mutation-positive melanoma who were assigned to 150 mg dabrafenib twice daily combined with 2 mg trametinib once daily in a phase I/II study showed a median overall survival (OS) of 23.8 months, compared with 20.2 months for patients assigned to dabrafenib alone [hazard ratio (HR)=0.73, 95% confidence interval (CI) 0.43-1.24; data cutoff March 2013], on the basis of an intention-to-treat analysis.
|
26340744 |
2015 |
|
rs121913377
|
|
melanoma
|
|
0.800 |
GeneticVariation
|
BEFREE |
Both melanomas carried the V600E BRAF mutation.
|
24942556 |
2014 |
|
rs121913377
|
|
melanoma
|
|
0.800 |
GeneticVariation
|
BEFREE |
Salmonella typhimurium A1-R targeting of a chemotherapy-resistant BRAF-V600E melanoma in a patient-derived orthotopic xenograft (PDOX) model is enhanced in combination with either vemurafenib or temozolomide.
|
28622068 |
2017 |
|
rs121913377
|
|
melanoma
|
|
0.800 |
GeneticVariation
|
BEFREE |
Immunohistochemistry as a quick screening method for clinical detection of BRAF(V600E) mutation in melanoma patients.
|
24563339 |
2014 |
|
rs121913377
|
|
melanoma
|
|
0.800 |
GeneticVariation
|
BEFREE |
We previously reported that rMETase, administrated by intra-peritoneal injection (ip-rMETase), could inhibit tumor growth in a patient-derived orthotopic xenograft (PDOX) model of a BRAF-V600E mutant melanoma.
|
29187018 |
2018 |
|
rs121913377
|
|
melanoma
|
|
0.800 |
GeneticVariation
|
BEFREE |
The BRAF V600E genotype and an absence of primary melanoma ulceration were also independently associated with longer PFS but not OS.
|
26218930 |
2015 |
|
rs121913377
|
|
melanoma
|
|
0.800 |
GeneticVariation
|
BEFREE |
Using primary melanocytes isolated directly from freshly excised human nevi naturally expressing the common BRAF(V600E)-activating mutation, nevi progressing to melanoma, and normal melanocytes engineered to inducibly express BRAF(V600E), we show that BRAF activation results in reversible, TGFβ-dependent, p15 induction that halts proliferation.
|
26183406 |
2015 |
|
rs121913377
|
|
melanoma
|
|
0.800 |
GeneticVariation
|
BEFREE |
Accurate detection of BRAF p.V600E mutations in challenging melanoma specimens requires stringent immunohistochemistry scoring criteria or sensitive molecular assays.
|
25228337 |
2014 |
|
rs121913377
|
|
melanoma
|
|
0.800 |
GeneticVariation
|
BEFREE |
Notably, the BRAF(V600E)</span> mutation is also present in 50-70% of melanomas.
|
26787892 |
2016 |
|
rs121913377
|
|
melanoma
|
|
0.800 |
GeneticVariation
|
BEFREE |
In conclusion, we used highly sensitive BRAF mutation detection methods and observed substantial evidence for heterogeneity of the BRAF(V600E) mutation within individual melanoma tumor specimens, and among multiple specimens from individual patients.
|
22235286 |
2012 |
|
rs121913377
|
|
melanoma
|
|
0.800 |
GeneticVariation
|
BEFREE |
MEK inhibitors are clinically active in BRAF(V600E) melanomas but only marginally so in KRAS mutant tumors.
|
24746704 |
2014 |
|
rs121913377
|
|
melanoma
|
|
0.800 |
GeneticVariation
|
BEFREE |
This study indicates that the V600</span>E mutation is present in metastatic melanomas and occurs more often in sites without chronic sun exposure.
|
20944096 |
2010 |
|
rs121913377
|
|
melanoma
|
|
0.800 |
GeneticVariation
|
BEFREE |
To anticipate possible resistance to ERK inhibitors (ERKi), we used SCH772984 (SCH) as a model ERKi to characterize resistance mechanisms in two BRAF V600E melanoma cell lines.
|
30833419 |
2019 |
|
rs121913377
|
|
melanoma
|
|
0.800 |
GeneticVariation
|
BEFREE |
CRAF inhibition induces apoptosis in melanoma cells with non-V600E BRAF mutations.
|
18794803 |
2009 |
|
rs121913377
|
|
melanoma
|
|
0.800 |
GeneticVariation
|
BEFREE |
Inhibition of SHH-GLI pathway by the novel small molecule inhibitor of smoothened NVP-LDE225 was followed by inhibition of cell growth and induction of apoptosis in human melanoma cell lines, interestingly with both BRAF(V600E</span>) and BRAF(Wild Type) status.
|
23935925 |
2013 |
|
rs121913377
|
|
melanoma
|
|
0.800 |
GeneticVariation
|
BEFREE |
This study thus defined SPRY4 as a potential mediator of synthetic suppression, which is likely to contribute to the observed exclusivity between BRAF(V600E) and NRAS(Q61R) mutations in melanoma.
|
30651601 |
2019 |
|
rs121913377
|
|
melanoma
|
|
0.800 |
GeneticVariation
|
BEFREE |
We detected Fn14 expression in ∼60% of the melanoma cell lines we tested, including both B-Raf WT and B-Raf(V600E) lines.
|
23190886 |
2013 |
|
rs121913377
|
|
melanoma
|
|
0.800 |
GeneticVariation
|
BEFREE |
Collectively, our findings implicate a new mechanism through which B-Raf(V600E) exerts its oncogenic effects in melanoma.
|
18071315 |
2008 |
|
rs121913377
|
|
melanoma
|
|
0.800 |
GeneticVariation
|
BEFREE |
Consistent with this prediction, combinations of I3C and Vemurafenib more potently inhibited melanoma cell proliferation and reduced MITF-M levels in BRAF-V600E expressing melanoma cells compared to the effects of each compound alone.
|
26878440 |
2017 |
|
rs121913377
|
|
melanoma
|
|
0.800 |
GeneticVariation
|
BEFREE |
The combination of a BRAF inhibitor dabrafenib and a MEK inhibitor trametinib (CombiDT) has improved outcomes compared with chemotherapy or BRAF inhibitor monotherapy in advanced BRAF V600E/K melanoma.
|
30661097 |
2019 |
|
rs121913377
|
|
melanoma
|
|
0.800 |
GeneticVariation
|
BEFREE |
Patients with rare <i>BRAF</i> mutations can respond to targeted therapy, however, efficacy seems to be lower compared with V600E mutated melanoma.
|
31580757 |
2019 |